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A new class of safe oligosaccharide polymer therapy to modify the mucus barrier of chronic respiratory disease

Pritchard, Manon, Powell, Lydia C., Menzies, Georgina, Lewis, Paul D., Hawkins, Karl, Wright, Chris, Doull, Iolo, Walsh, Timothy R., Onsoyen, Edvar, Dessen, Arne, Myrvold, Rolf, Rye, P. D., Myrset, A. H., Stevens, Howard N. E., Hodges, Lee A., MacGregor, Gordon, Neilly, James B., Hill, Katja E. and Thomas, David W. 2016. A new class of safe oligosaccharide polymer therapy to modify the mucus barrier of chronic respiratory disease. Molecular Pharmaceutics 13 (3) , pp. 863-872. 10.1021/acs.molpharmaceut.5b00794

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Abstract

The host- and bacteria-derived extracellular polysaccharide coating of the lung is a considerable challenge in chronic respiratory disease and is a powerful barrier to effective drug delivery. A low molecular weight 12–15-mer alginate oligosaccharide (OligoG CF-5/20), derived from plant biopolymers, was shown to modulate the polyanionic components of this coating. Molecular modeling and Fourier transform infrared spectroscopy demonstrated binding between OligoG CF-5/20 and respiratory mucins. Ex vivo studies showed binding induced alterations in mucin surface charge and porosity of the three-dimensional mucin networks in cystic fibrosis (CF) sputum. Human studies showed that OligoG CF-5/20 is safe for inhalation in CF patients with effective lung deposition and modifies the viscoelasticity of CF-sputum. OligoG CF-5/20 is the first inhaled polymer therapy, represents a novel mechanism of action and therapeutic approach for the treatment of chronic respiratory disease, and is currently in Phase IIb clinical trials for the treatment of CF.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Dentistry
Additional Information: ACS AuthorChoice - This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes
Publisher: American Chemical Society
ISSN: 1543-8384
Funders: Algipharma
Date of First Compliant Deposit: 4 May 2016
Date of Acceptance: 1 February 2016
Last Modified: 22 Jun 2019 21:43
URI: http://orca.cf.ac.uk/id/eprint/86319

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